The skin of congenic haired and hairless HRS/J mice has been established as a model in which to study determinants of dioxin induced toxicity. Both genotypes carry high affinity cytosol receptor and respond to dioxin exposure with the induction of epidermal aryl hydrocarbon hydroxylase activity. In addition, skin of the hairless (hr/hr), but not of the haired (hr/+ or +/+), mice responds to dioxin exposure with well defined pattern of morphologic changes. It has been proposed that in the hr/hr genotype, dioxin activates an additional battery of genes associated with proliferative/metaplastic skin changes, and that this activation is under genetic control (at the hr locus). This proposal outlines studies to pursue this hypothesis by further comparing the changes in cutaneous morphology and biochemical reactions in skin of congenic HRS/J mice in vivo and in vitro in response to dioxin exposure. Some of the specific biochemical reactions proposed for study are: epidermal ornithine decarboxylase, S-adenosyl methionine decarboxylase, and epidermal transglutaminase activity, cutaneous lipid biosynthesis, DNA synthesis, effect of anti-inflammatory agents on the above parameters, and localization of sites of disposition of dioxin in skin using autoradiographic studies.